1. Chapter 12
The Cell Cycle

2. Overview: The Key Roles of Cell Division
The ability of organisms to produce more of their own kind best distinguishes living things from nonliving matter
The continuity of life is based on the reproduction of cells, or cell division
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3. Multicellular organisms depend on cell division for
In unicellular organisms, division of one cell reproduces the entire organism
Multicellular organisms depend on cell division for
Development from a fertilized cell
Growth
Repair
Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division
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4. Concept 12.1: Most cell division results in genetically identical daughter cells
Most cell division results in daughter cells with identical genetic information, DNA
The exception is meiosis, a special type of division that can produce sperm and egg cells
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5. Cellular Organization of the Genetic Material
All the DNA in a cell constitutes the cell’s genome
A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells)
DNA molecules in a cell are packaged into chromosomes
20 m
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6. Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division
Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus
Somatic cells (nonreproductive cells) have two sets of chromosomes
Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells
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7. Distribution of Chromosomes During Eukaryotic Cell Division
In preparation for cell division, DNA is replicated and the chromosomes condense
Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), which separate during cell division
The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached
0.5 m
Centromere
Sister chromatids
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8. Once separate, the chromatids are called chromosomes
During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei
Once separate, the chromatids are called chromosomes
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9. Chromosomal DNA molecules
Figure
Chromosomal DNA molecules
Chromosomes 1
Centromere
Chromosome arm
Chromosome duplication (including DNA replication) and condensation 2
Sister chromatids
Figure 12.5 Chromosome duplication and distribution during cell division.
Separation of sister chromatids into two chromosomes 3

10. Eukaryotic cell division consists of
Mitosis, the division of the genetic material in the nucleus
Cytokinesis, the division of the cytoplasm
Gametes are produced by a variation of cell division called meiosis
Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell
Cytokinesis
Mitosis rap
Crash course
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11. Do now
Compare cytokinesis to animal cells and plant cells.

12. Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis
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13. Phases of the Cell Cycle
INTERPHASE G1 G2
S (DNA synthesis)
MITOTIC (M) PHASE
Cytokinesis
Mitosis
The cell cycle consists of
Mitotic (M) phase (mitosis and cytokinesis)
Interphase (cell growth and copying of chromosomes in preparation for cell division)
Interphase (about 90% of the cell cycle) can be divided into subphases
G1 phase (“first gap”)
S phase (“synthesis”)
G2 phase (“second gap”)
The cell grows during all three phases, but chromosomes are duplicated only during the S phase
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14. Chromosome, consisting of two sister chromatids
Mitosis is conventionally divided into five phases
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis overlaps the latter stages of mitosis
G2 of Interphase
Prophase
Prometaphase
Centrosomes (with centriole pairs)
Chromatin (duplicated)
Nucleolus
Nuclear envelope
Plasma membrane
Early mitotic spindle
Aster
Centromere
Chromosome, consisting of two sister chromatids
Fragments of nuclear envelope
Nonkinetochore microtubules
Kinetochore
Kinetochore microtubule
Metaphase
Metaphase plate
Anaphase
Telophase and Cytokinesis
Spindle
Centrosome at one spindle pole
Daughter chromosomes
Cleavage furrow
Nucleolus forming
Nuclear envelope forming
10 m
For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files.
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15. Chromosome, consisting of two sister chromatids
Figure 12.7a
G2 of Interphase
Prophase
Prometaphase
Centrosomes (with centriole pairs)
Fragments of nuclear envelope
Chromatin (duplicated)
Early mitotic spindle
Aster
Nonkinetochore microtubules
Centromere
Figure 12.7 Exploring: Mitosis in an Animal Cell
Plasma membrane
Nucleolus
Kinetochore
Kinetochore microtubule
Chromosome, consisting of two sister chromatids
Nuclear envelope

16. Metaphase Anaphase Telophase and Cytokinesis Metaphase plate
Figure 12.7b
Metaphase
Anaphase
Telophase and Cytokinesis
Metaphase plate
Cleavage furrow
Nucleolus forming
Figure 12.7 Exploring: Mitosis in an Animal Cell
Nuclear envelope forming
Spindle
Centrosome at one spindle pole
Daughter chromosomes

17. The Mitotic Spindle: A Closer Look
The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis
In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center
The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase
For the Cell Biology Video Spindle Formation During Mitosis, go to Animation and Video Files.
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18. An aster (a radial array of short microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters
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19. Kinetochores are protein complexes associated with centromeres
During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes
Kinetochores are protein complexes associated with centromeres
At metaphase, the chromosomes are all lined up at the metaphase plate, an imaginary structure at the midway point between the spindle’s two poles
Sister chromatids
Aster
Centrosome
Metaphase plate (imaginary)
Kineto- chores
Overlapping nonkinetochore microtubules
Kinetochore microtubules
Microtubules
Chromosomes
0.5 m
1 m
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20. The microtubules shorten by depolymerizing at their kinetochore ends
Chromosome movement
Microtubule
Motor protein
Chromosome
Kinetochore
Tubulin subunits
Mark
Spindle pole
EXPERIMENT
RESULTS
CONCLUSION
In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell
The microtubules shorten by depolymerizing at their kinetochore ends
For the Cell Biology Video Microtubules in Anaphase, go to Animation and Video Files.
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21. Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell
In telophase, genetically identical daughter nuclei form at opposite ends of the cell
Cytokinesis begins during anaphase or telophase and the spindle eventually disassembles
For the Cell Biology Video Microtubules in Cell Division, go to Animation and Video Files.
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22. Cytokinesis: A Closer Look
In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
In plant cells, a cell plate forms during cytokinesis
Video: Animal Mitosis
Video: Sea Urchin (Time Lapse)
Animation: Cytokinesis
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23. (a) Cleavage of an animal cell (SEM)
Figure 12.10
(a) Cleavage of an animal cell (SEM)
(b) Cell plate formation in a plant cell (TEM)
100 m
Cleavage furrow
Vesicles forming cell plate
Wall of parent cell
1 m
Cell plate
New cell wall
Figure Cytokinesis in animal and plant cells.
Contractile ring of microfilaments
Daughter cells
Daughter cells

24. Chromatin condensing Nucleus 10 m Nucleolus Chromosomes Cell plate 1
Figure 12.11
Chromatin condensing
Nucleus
10 m
Nucleolus
Chromosomes
Cell plate
Figure Mitosis in a plant cell. 1
Prophase 2
Prometaphase 3
Metaphase 4
Anaphase 5
Telophase

25. Binary Fission in Bacteria
Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission
In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart
The plasma membrane pinches inward, dividing the cell into two
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26. Chromosome replication begins. Two copies of origin
Figure
Origin of replication
Cell wall
Plasma membrane
E. coli cell
Bacterial chromosome 1
Chromosome replication begins.
Two copies of origin 2
Replication continues.
Origin
Origin 3
Replication finishes.
Figure Bacterial cell division by binary fission. 4
Two daughter cells result.

27. The Evolution of Mitosis
Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission
Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis
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28. Intact nuclear envelope Chromosomes
(a) Bacteria
(b) Dinoflagellates
(d) Most eukaryotes
Intact nuclear envelope
Chromosomes
Microtubules
Kinetochore microtubule
Fragments of nuclear envelope
Bacterial chromosome
(c)
Diatoms and some yeasts
Figure 12.13
Figure Mechanisms of cell division in several groups of organisms.

29. Do now
How many cells are in each stage of mitosis? (prophase, prometaphase, metaphase, anaphase and telophase)

30. Telophase and Cytokinesis
Mitosis
Cytokinesis
MITOTIC (M) PHASE G1 G2 S
Telophase and Cytokinesis
Anaphase
Metaphase
Prometaphase
Prophase I T R HA E P N
Review 12.2

31. Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system
The frequency of cell division varies with the type of cell
These differences result from regulation at the molecular level
Cancer cells manage to escape the usual controls on the cell cycle
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32. Evidence for Cytoplasmic Signals
Experiment 1
Experiment 2 S G1 M
EXPERIMENT
RESULTS
When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase—DNA was synthesized.
When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.
The cell cycle appears to be driven by specific chemical signals present in the cytoplasm
Some evidence for this hypothesis comes from really cool experiments!
INTERPHASE G1 G2
S (DNA synthesis)
MITOTIC (M) PHASE
Cytokinesis
Mitosis
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33. The Cell Cycle Control System
The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
The cell cycle control system is regulated by both internal and external controls
The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received
G1 checkpoint G1 G2
G2 checkpoint
M checkpoint M S
Control system
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34. For many cells, the G1 checkpoint seems to be the most important
If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide
If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase
G1 checkpoint G1 G0
(a) Cell receives a go-ahead signal.
(b) Cell does not receive a go-ahead signal.
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35. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases
Cyclin accumulation
(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle
MPF activity
Cyclin concentration
Time M S G1 G2
Cdk
Degraded cyclin
Cyclin is degraded
MPF
G2 checkpoint
Cyclin
Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)
Cdks activity fluctuates during the cell cycle because it is controled by cyclins
MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase
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36. Stop and Go Signs: Internal and External Signals at the Checkpoints
Internal signal
kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase
External signal
growth factors, proteins released by certain cells that stimulate other cells to divide
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37. Figure 12.18
For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture 1
A sample of human connective tissue is cut up into small pieces.
Scalpels
Petri dish 2
Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 4
10 m
PDGF is added to half the vessels. 3
Cells are transferred to culture vessels.
Figure The effect of platelet-derived growth factor (PDGF) on cell division.
Without PDGF
With PDGF

38. A clear example of external signals is density-dependent inhibition, in which crowded cells stop dividing
Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide
Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence
They don’t care, they divide no matter what
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39. Density-dependent inhibition
Figure 12.19
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
Figure Density-dependent inhibition and anchorage dependence of cell division.
20 m
20 m
(a) Normal mammalian cells
(b) Cancer cells

40. Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not respond normally to the body’s control mechanisms
Cancer cells may not need growth factors to grow and divide
They may make their own growth factor
They may convey a growth factor’s signal without the presence of the growth factor
They may have an abnormal cell cycle control system
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41. A normal cell is converted to a cancerous cell by a process called transformation
Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue
If abnormal cells remain only at the original site, the lump is called a benign tumor
Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors
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42. Figure 12.20
Lymph vessel
Tumor
Blood vessel
Cancer cell
Glandular tissue
Metastatic tumor 1
A tumor grows from a single cancer cell. 2
Cancer cells invade neighboring tissue. 3
Cancer cells spread through lymph and blood vessels to other parts of the body. 4
Cancer cells may survive and establish a new tumor in another part of the body.
Figure The growth and metastasis of a malignant breast tumor.
Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment